Drug Profile | Ethosuximide

ethosuximide pharmacology


As part of your pharmacy license exam, candidates are expected to have a thorough, rounded knowledge of the clinical pharmacology of anticonvulsant drugs. Today, we review the theory behind ethosuximide you need to know.

There are many anticonvulsant drugs and it’s often difficult to commit these drugs to memory. There are almost three dozen classes – each with their own indication, mechanism, side effect, dosage and drug interaction profiles.

It’s best to focus on one drug / drug class at a time. Otherwise, you will become overwhelmed by the subject. Today, we talk about ethosuximide, an important medicine that has only one indication – absence seizures (petit mal seizures) – seizures characterised by brief loss / return of consciousness.

Unlike other forms of seizure, such as grand mal seizures, absence seizures are typically not associated with what it known as a postictal state – the name ascribed to the lethargy and altered state of consciousness that patients experience in the immediate post-seizure phase.

The drug is not used in the treatment of any other seizure type.

Ethosuximide trades as Zarontin – a drug that was approved by the FDA in 1960.

Below, then, we talk about how ethosuximide works, what side effects and drug interactions its linked to, as well as what aspects of clinical pharmacy – such as dosage – you are expected to know.

Let’s get started.

Mechanism of action

All anticonvulsant drugs impact neuronal excitability. Zarontin is no different.

Ethosuximide works by interacting with, and blocking, T-type calcium channels. Its mechanism is not limited to this effect. Initial studies failed to replicate the therapeutic validity of this proposed mechanism. However, later studies robustly substantiated the claim that ethosuximide blocks all T-type channel isoforms.

By blocking these calcium channels, ethosuximide works to stabilise electrical activity in the brain.

Though it is believed to work by this means, it’s precise mechanism of action is not yet fully understood.

Ethosuximide belongs to the succinimide class of antiepileptic drugs.

Side effects

Side effects with ethosuximide include:

  • Drowsiness
  • Dizziness
  • Fatigue
  • Loss of appetite
  • Diarrhea
  • Weight loss
  • Nausea / vomiting
  • Headache
  • Loss of coordination
  • Hiccups

Some patients experience more serious effects, such as tongue / gum swelling, suicidal ideation / depression, cytopenia and lupus erythematosus.

This is not an exhaustive list. Patients may experience side effects not listed here.


Here are the standard recommended dosages for ethosuximide:

  • Adult Dose for Seizures: initial dose of 500mg orally once daily.
  • This dose should be gradually increased, typically by 250mg per day every 4-7 days until optimum therapy / side effect management has been attained.
  • Maintenance dose therefore depends on patient response.
  • Optimum therapeutic plasma range: 40-100mcg/mL.
  • Doses higher than 1.5g per day require medical supervision.
  • Pediatric Dose for Seizures: initial dose varies according to age:
  • 3-6 years old: 250mg orally once daily
  • 6 years and older: 500mg orally once daily
  • Dose should be increased gradually until optimum dose achieved – for example: 250mg additions every 4-7 days.
  • Optimum dose for pediatric patients:
  • 20mg/kg/day or 40mg/kg/day have found to provide optimum therapy.

These are not strict guidelines but are instead recommendations.

Dosages may differ depending on patient profile / clinical circumstances.

Clinical pharmacology

Here are some of the key factors of clinical pharmacology of ethosuximide you need to know:

  • Ethosuximide is first line for absence seizures. It is preferred over valproate because it lacks the hepatotoxicity risk associated with valproate.
  • Ethosuximide use should not be stopped suddenly as this may increase the risk of seizures.
  • Ethosuximide affects alertness. Patients should be informed that caution is necessary before engaging in activities such as driving, machinery use or any other activity risk that requires concentration.
  • Ethosuximide should not be given to a child less than 3 years old.
  • Ethosuximide is primarily metabolised by CYP 3A4, though it is partially metabolised by CYP 2E1.
  • Zarontin is only available for administration via the oral route (capsules / solution).
  • Ethosuximide may elevate serum phenytoin levels.

Zarontin remains an important medicine in the treatment of absence seizures.

Here, we’ve combed through the fundamental clinical pharmacology you are expected to know for your pharmacy exam. Of course, ethosuximide is one of many anticonvulsant drugs to study.

It’s vital that you take the same study care with every other drug class. It’s time-consuming but, with enough effort, you may be surprised how easy and management this section can become.

NAPLEX Study Guide is the leading online resource to help pharmacy graduates pass their exams. Check back to our blog soon for even more great tips, tricks and drug summaries to help you pass your next pharmacy exam.


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